Genetic and transcriptomic analyses provide new insights on the early antiviral response to VHSV in resistant and susceptible rainbow trout

Abstract

BackgroundThe viral hemorrhagic septicemia virus (VHSV) is a major threat for salmonid farming and for wild fish populations worldwide. Previous studies have highlighted the importance of innate factors regulated by a major quantitative trait locus (QTL) for the natural resistance to waterborne VHSV infection in rainbow trout. The aim of this study was to analyze the early transcriptomic response to VHSV inoculation in cell lines derived from previously described resistant and susceptible homozygous isogenic lines of rainbow trout to obtain insights into the molecular mechanisms responsible for the resistance to the viral infection.ResultsWe first confirmed the presence of the major QTL in a backcross involving a highly resistant fish isogenic line (B57) and a highly susceptible one (A22), and were able to define the confidence interval of the QTL and to identify its precise position. We extended the definition of the QTL since it controls not only resistance to waterborne infection but also the kinetics of mortality after intra-peritoneal injection. Deep sequencing of the transcriptome of B57 and A22 derived cell lines exposed to inactivated VHSV showed a stronger response to virus inoculation in the resistant background. In line with our previous observations, an early and strong induction of interferon and interferon-stimulated genes was correlated with the resistance to VHSV, highlighting the major role of innate immune factors in natural trout resistance to the virus. Interestingly, major factors of the antiviral innate immunity were much more expressed in naive B57 cells compared to naive A22 cells, which likely contributes to the ability of B57 to mount a fast antiviral response after viral infection. These observations were further extended by the identification of several innate immune-related genes localized close to the QTL area on the rainbow trout genome.ConclusionsTaken together, our results improve our knowledge in virus-host interactions in vertebrates and provide novel insights in the molecular mechanisms explaining the resistance to VHSV in rainbow trout. Our data also provide a collection of potential markers for resistance and susceptibility of rainbow trout to VHSV infection.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4860-1) contains supplementary material, which is available to authorized users.

Quantitative trait loci for resistance to Flavobacterium psychrophilum in rainbow trout: effect of the mode of infection and evidence of epistatic interactions

“…At INRA, we have established a collection of 16 isogenic homozygous rainbow trout lines that were derived from the INRA SY rainbow trout population after two generations of gynogenetic reproduction and further propagated by within-line single pair mating [ 43 ]. The lines have been screened for resistance to various diseases including several viruses [ 43 – 45 ] and more recently, for resistance to F. psychrophilum , using either injection or immersion as routes of infection [ 46 , and unpublished results].…”

“…Homozygosity for each F2 individual was checked on the 11,570 remaining loci and 24 fish were found to have a heterozygosity rate higher than 1%. Previous studies performed on isogenic lines [ 45 , 49 ] assumed that residual heterozygous loci may be due to unreduced ova, donor milt contamination, mutation or sequencing errors. We did not find any F2 individual that was heterozygous at loci where the two grandparents shared the same allele, so contamination by donor milt was excluded.…”

Resistance of pearlspot larvae, Etroplus suratensis, to redspotted grouper nervous necrosis virus by immersion challenge

“…However, the function of Rtp3 in pearlspot with respect to viral disease resistance has not been studied. The resistance to viral infections may involve multiple mechanisms including genetic background and capacity to mount an early interferon response (Verrier et al, ). It will be imperative to study the resistance mechanism in pearlspot to NNV which will help in formulating control measures for this lethal virus.…”

Combining Multiple Approaches and Models to Dissect the Genetic Architecture of Resistance to Infections in Fish

“…Deep sequencing of the transcriptome of one resistant (the same B57 line) and one susceptible cell line after stimulation with inactivated VHSV revealed a stronger and earlier response in the resistant background (Verrier et al, 2018). Many typical interferon-stimulated genes were induced, such as irf1, rsad2, and members of the ifi44, gig, parp, ifit, and cd9 families, as well as many fintrim genes.…”

“…CMS, cardiomyopathy syndrome; AGD, amoebic gill disease; BCWD, bacterial cold water disease; VHS, viral hemorrhagic septicemia; IPN, infectious pancreatic necrosis; INH, infectious hematopoietic necrosis; ISA, infectious salmon anemia; SRS, salmonid rickettsial septicemia; CyHV-3, cyprinid herpesvirus; QTL, quantitative trait loci; GWAS, genome-wide association study. References: 1 Boison et al, 2019a ; 2 Hillestad and Moghadam, 2019 ; 3 Boison et al, 2019b ; 4 Fraslin et al, 2018 ; 5 Rodríguez-Ramilo et al, 2014 ; 6 Houston et al, 2008 ; 7 Houston et al, 2010 ; 8 Houston et al, 2012 ; 9 Gheyas et al, 2010 ; 10 Moen et al, 2009 ; 11 Moen et al, 2015 ; 12 Verrier et al, 2013a ; 13 Saura et al, 2019 ; 14 Langevin et al, 2012 ; 15 Marancik et al, 2015 ; 16 Paneru et al, 2016 ; 17 Zwollo et al, 2017 ; 18 Moore et al, 2018 ; 19 Dettleff et al, 2015 ; 20 Reyes-López et al, 2015 ; 21 Robledo et al, 2016 ; 22 Sutherland et al, 2014 ; 23 Braden et al, 2015 ; 24 Holm et al, 2015 ; 25 Verrier et al, 2018 ; 26 Dehler et al, 2019 ; 27 Gratacap et al, 2019 ; 28 Palaiokostas et al, 2018b ; 29 Robledo et al, 2019 ; 30 Verrier et al, 2012 ; 31 Verrier et al, 2013b ; 32 Biacchesi et al, 2007 32 .…”